Since its inception the Yeast Resource Center has specialized in extracting information about protein function from genome sequence. We began when the first eukaryotic genome was completed (budding yeast) and developed an array of technologies to decipher protein function from genome sequence. In this application, we make the natural progression towards understanding how protein variation affects protein levels, modification, function and structure. We propose to develop technologies in four areas: 1) To identify different protein variants or isoforms. 2) To quantify proteins by mass spectrometry with a focus on determining absolute levels of a protein. 3) To study how protein variation affects protein function. 4) To determine the structures of protein complexes not amenable to high-resolution methods such as x-ray crystallography and NMR.